Similar Decreases In Heart Rate Research Articles

Ivabradine and Bisoprolol on Doppler-derived Coronary Flow Velocity Reserve in Patients with Stable Coronary Artery Disease: Beyond the Heart Rate.

IntroductionCoronary flow velocity reserve (CFVR) is an important prognostic marker in patients with stable coronary artery disease (CAD). Beta-blockers and ivabradine have been shown to improve CFVR in patients with stable CAD, but their effects were never compared. The aim of the current study was to compare the effects of bisoprolol and ivabradine on CFVR in patients with stable CAD.MethodsPatients in sinus rhythm with stable CAD were enrolled in this prospective, randomized, double-blind trial. Patients had to be in a stable condition for at least 15 days before enrollment, on their usual therapy. Patients who were receiving beta-blockers or ivabradine entered a 2-week washout period from these drugs before randomization. Transthoracic Doppler-derived CFVR was assessed in left anterior descending coronary artery, and was calculated as the ratio of hyperemic to baseline diastolic coronary flow velocity (CFV). Hyperemic CFV was obtained using dipyridamole administration using standard protocols. After CFVR assessment, patients were randomized to ivabradine or bisoprolol and entered an up-titration phase, and CFVR was assessed again 1 month after the end of the up-titration phase.ResultsFifty-nine patients (38 male, 21 female; mean age 69 ± 9 years) were enrolled. Transthoracic Doppler-derived assessment of CFV and CFVR was successfully performed in all patients. Baseline characteristics were similar between the bisoprolol and ivabradine groups. No patient dropped out during the study. At baseline, rest and hyperemic peak CFV as well as CFVR was not significantly different in the ivabradine and bisoprolol groups. After the therapy, resting peak CFV significantly decreased in both the ivabradine and bisoprolol groups, but there was no significant difference between the groups (ivabradine group 20.7 ± 4.6 vs. 22.8 ± 5.2, P < 0.001; bisoprolol group 20.1 ± 4.1 vs. 22.1 ± 4.3, P < 0.001). However, hyperemic peak CFV significantly increased in both groups, but to a greater extent in patients treated with ivabradine (ivabradine: 70.7 ± 9.4 vs. 58.8 ± 9.2, P < 0.001; bisoprolol: 65 ± 8.3 vs. 58.7 ± 8.2, P < 0.001). Accordingly, CFVR significantly increased in both groups (ivabradine 3.52 ± 0.64 vs. 2.67 ± 0.55, P < 0.001; bisoprolol 3.35 ± 0.70 vs. 2.72 ± 0.55, P < 0.001), but it was significantly higher in ivabradine group, despite a similar decrease in heart rate (63 ± 7 vs. 61 ± 6; P not significant).ConclusionIvabradine improves hyperemic peak CFV and CFVR to a greater extent than bisoprolol in patients with stable CAD, despite a similar decrease in heart rate. These data demonstrate that the benefits from ivabradine therapy go beyond the heart rate. This could be due to a different mechanism such as diastolic perfusion time, isovolumic ventricular relaxation, end-diastolic pressure, and collaterals.FundingServier.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-015-0237-x) contains supplementary material, which is available to authorized users.

Nebivolol Exerts Beneficial Effects on Endothelial Function, Early Endothelial Progenitor Cells, Myocardial Neovascularization, and Left Ventricular Dysfunction Early After Myocardial Infarction Beyond Conventional β1-Blockade

The aim of this study was to investigate whether nebivolol has added effects on left ventricular (LV) dysfunction and remodeling early after myocardial infarction (MI) beyond its β₁-receptor-blocking properties. Nebivolol is a third-generation selective β₁-adrenoreceptor antagonist that stimulates endothelial cell nitric oxide (NO) production and prevents vascular reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation. Both endothelial NO synthase-derived NO production and NADPH oxidase activation are critical modulators of LV dysfunction early after MI. Mice with extensive anterior MI (n = 90) were randomized to treatment with nebivolol (10 mg/kg/day), metoprolol-succinate (20 mg/kg/day), or placebo for 30 days starting on day 1 after surgery. Infarct size was similar among the groups. Both β₁-adrenergic receptor antagonists caused a similar decrease in heart rate. Nebivolol therapy improved endothelium-dependent vasorelaxation and increased early endothelial progenitor cells 4 weeks after MI compared with metoprolol and placebo. Nebivolol, but not metoprolol, inhibited cardiac NADPH oxidase activation after MI, as detected by electron spin resonance spectroscopy analysis. Importantly, nebivolol, but not metoprolol, improved LV dysfunction 4 weeks after MI (LV ejection fraction: nebivolol vs. metoprolol vs. placebo: 32 ± 4% vs. 17 ± 6% vs. 19 ± 4%; nebivolol vs. metoprolol: p < 0.05) and was associated with improved survival 4 weeks post-MI compared with placebo. Nebivolol had a significantly more pronounced inhibitory effect on cardiomyocyte hypertrophy after MI compared with metoprolol. Nebivolol improves LV dysfunction and survival early after MI likely beyond the effects provided by conventional β₁-receptor blockade. Nebivolol induced effects on NO-mediated endothelial function, early endothelial progenitor cells and inhibition of myocardial NADPH oxidase likely contribute to these beneficial effects of nebivolol early after MI.

Atenolol vs. propranolol in essential tremor A controlled, quantitative study

The beta-1 selective, hydrophilic adrenoceptor blocking drug atenolol (100 mg daily) was compared to the non-selective, lipid-soluble beta-blocker propranolol (240 mg daily), and to placebo, in a double-blind cross-over study in 24 patients with essential tremor. Atenolol and propranolol caused a similar decrease in heart rate. Both beta-blockers also suppressed the tremor intensity; there was no significant difference between them, but both were significantly better than placebo. These drugs did not affect tremor frequency. Twelve of the patients preferred propranolol subjectively, one preferred atenolol and none preferred placebo. No marked side-effects were observed. It was concluded that atenolol and other cardio-selective blockers offer an alternative for patients unable to tolerate the non-selective drugs. The site of action and receptor sub-type involved have still to be determined.

Comparative effects of ivabradine, a selective heart rate‐lowering agent, and propranolol on systemic and cardiac haemodynamics at rest and during exercise

To compare in humans the effects of ivabradine and propranolol on cardiac and systemic haemodynamics at rest, during tilt and exercise. Nine healthy volunteers randomly received single oral doses of ivabradine (Iva, 30 mg), propranolol (Propra, 40 mg) or placebo (Plac) during a double-blind cross-over study. Doses were selected to be equipotent in heart rate (HR) reduction. HR, systolic and diastolic blood pressure (SBP, DBP), cardiac index (CI, bioimpedance), rate pressure product (RPP), plasma epinephrine (E) and norepinephrine (NE), were measured at rest at baseline, before and after two tilt and exercise tests, started 2 and 5 h after drug intake. Heart rate variability (low to high frequency ratio LF/HF) was evaluated at rest and at 5 th minute of tilt. At rest, HR and RPP decreased similarly with Iva and Propra (both P < 0.01). During tilt, HR increased less with Iva than Propra (P < 0.01), LF/HF decreased after Iva (P < 0.03), SBP and mean blood pressure decreased after Propra (both P < 0.01), RPP decreased similarly after Iva and Propra (both P < 0.01) and CI decreased to a greater extent with Propra than with Iva or Plac (both P < 0.04). During exercise, Iva and Propra similarly decreased HR (both P < 0.01) and RPP (P < 0.01). These results demonstrate that for a similar decrease in HR at rest and during sympathetic stimulation, acute administration of ivabradine, a selective heart rate-lowering agent, decreased myocardial oxygen demand to the same extent as a reference beta-blocker, propranolol, but without evidence of depressant effect on cardiac function.

Autonomic Effects of Nebivolol versus Atenolol in Healthy Subjects

Nitric oxide may stimulate sympathoinhibitory reflexes. Nebivolol is a beta(1) selective adrenergic receptor antagonist with ancillary vasodilating properties by modulating nitric oxide secretion. We investigated whether nebivolol affects autonomic function differently compared with atenolol, another selective beta(1)-blocker without vasorelaxant actions. Fourteen healthy volunteers (9 men, 5 women; 25 +/- 3.7 years) received single oral doses of 5 mg nebivolol, 50 mg atenolol, and 100 mg atenolol, each taken for a 2-week period. Heart rate variability (HRV) measurements in time- (SDNN; rMSSD; pNN50) and frequency-domain (low frequency-LF; high frequency-HF; LF/HF ratio) were used to study the autonomic effects of the three regimens on the same patients from serial 24-hour ECGs. Both nebivolol and atenolol, the 50 mg dose as well as the 100 mg dose, produced similar decreases in heart rate compared with baseline throughout the 24-h period (from 82 +/- 9 beats/min to 72 +/- 7 beats/min, 69 +/- 9, and 68 +/- 8 beats/min, respectively, p < 0.001). Overall, the administration of each beta -blocker led to directionally similar increases in the HRV variables, which were most significant following 100 mg atenolol. Nebivolol and the 50 mg dose of atenolol produced similar increases in rMSSD and pNN50 during the entire 24-h period, and in HF power, particularly during the nighttime (p < 0.05). However, the coefficient of HF variance resulted in similar values after either beta -blocker regimen. The LF/HF ratio was most reduced throughout the 24-h period following 100 mg atenolol (p < 0.001), and to a similar extent decreased in the nighttime following nebivolol and atenolol 50 mg (p < 0.01). Nebivolol 5 mg exerts similar effects on time and frequency domain indexes of HRV as 50 mg atenolol. Nebivolol attenuates sympathetic tone, but does not appear to promote vagal activity more than atenolol.

Vergleich der Effekte von endotrachealem Absaugen und Surfactantapplikation auf Hämodynamik und Oxygenierung Frühgeborener - Eine Nahinfrarotspektroskopie-Studie1

Aim of this study was to assess whether the decrease in heart rate and oxygen saturation occurring acutely after bolus administration of surfactant is different from the effect of endotracheal suctioning and whether there are effects on cerebral haemodynamics and oxygenation. Twelve premature infants, birth weight 720-1560 g (Median 935 g), gestational age 25-30 weeks (Median 28 weeks), were investigated during surfactant administration (Curosurf) as a single bolus and a preceding endotracheal suctioning procedure. Using near infrared spectroscopy changes in cerebral blood volume and cerebral oxygenation index were assessed. Heart rate, arterial oxygen saturation, PCO2, and arterial blood pressure were registered continuously. Data were compared at 30, 60 and 120 seconds after the beginning of suctioning and surfactant administration. Endotracheal suctioning and surfactant administration induced a similar decrease in heart rate (-29/min, SD 25, p < 0.01 and -30/min, SD 23, p < 0.001) during the first 30 seconds and in oxygen saturation at the 30 seconds datapoint (-3%, SD 2, p < 0.01 and -3%, SD 6, p < 0.05). The decrease in oxygen saturation persisted at 60 seconds after the start of suctioning (-4%, SD 5, p < 0.05). In contrast, oxygen saturation was no longer different from baseline levels 60 seconds after surfactant administration (+1%, SD 6, p = 0.5). After suctioning, cerebral oxygenation index had decreased significantly from baseline levels at 30, 60, and 120 seconds. In contrast, after surfactant administration, no significant difference from baseline was noted at 30 and 60 seconds and a significant increase occurred at 120 seconds. Mean arterial blood pressure, PCO2, and cerebral blood volume did not change significantly during endotracheal suctioning and during surfactant administration. Acute decreases in heart rate and oxygen saturation during bolus administration of surfactant are equal to effects occurring during endotracheal suctioning. However, the decrease in oxygen saturation is shorter and more importantly, no decrease in cerebral oxygenation occurs.

Effect of carvedilol in comparison with metoprolol on myocardial collagen postinfarction

OBJECTIVESWe sought to compare the effects of two different beta-blockers, carvedilol and metoprolol, to an angiotensin-converting enzyme (ACE) inhibitor (captopril) on myocardial collagen deposition during healing and ventricular remodeling after myocardial infarction (MI).BACKGROUNDBeta-adrenergic blockade has been shown to be beneficial post-MI and in chronic heart failure. Carvedilol is a new-generation vasodilating beta-blocker with additional alpha1-adrenoceptor antagonism and an antiproliferative action, but it is not known if it is more beneficial than standard selective beta-blockers.METHODSUsing a rat model of MI, induced by left coronary ligation, we studied the effects of 11 weeks of therapy with oral carvedilol, metoprolol or captopril on hemodynamics, tissue weights, collagen volume fraction and hydroxyproline content.RESULTSBoth beta-blockers caused similar decreases in heart rate and LVEDP compared with untreated post-MI rats. At equivalent beta-adrenoceptor blocking doses, however, carvedilol, but not metoprolol, attenuated the increase in collagen content in noninfarcted regions and prevented the increase in right ventricular weight/body weight (all p < 0.05), and its effect was similar to captopril. Metoprolol treatment tended to increase right ventricular weight and heart weight (p < 0.05). There were no differences in infarct size between the groups.CONCLUSIONSLong-term treatment with both beta-blockers, as well as an ACE inhibitor, benefited the healing process in rats post-MI. At equivalent myocardial beta-adrenoceptor blocking doses, however, carvedilol significantly reduced myocardial collagen in the noninfarcted myocardium and cardiac hypertrophy in the right ventricle, whereas metoprolol had no effect on myocardial collagen deposition.

Effects of age and hypertension on cardiac responses to the α 1-agonist phenylephrine in humans

Both aging and hypertension decrease the responsiveness of several receptor systems. The purpose of this study was to investigate the effect of aging versus hypertension on the blood pressure (BP), heart rate, and left ventricular (LV) responses to the α 1-agonist phenylephrine in humans. Fourteen young (age, 21–40 years; range, 30 ± 1 years; mean ± SEM), and 18 older (age, 50–73 years; range, 60 ± 1 years) healthy volunteers, as well as 10 young (age, 30–39 years; range, 36 ± 1 years) and 15 older (age, 50– 64 years; range, 58 ± 1 years) hypertensive subjects were studied. Phenylephrine was administered at four incremental rates for 8 min each. Cardiac responses were assessed by echocardiography. Phenylephrine caused twofold larger increases in systolic BP in young and older hypertensives and older normotensives, compared with young normotensives, but similar decreases in heart rate in all four groups. Younger normotensive subjects exhibited the largest decreases in stroke volume index, ejection fraction, and cardiac index in response to phenylephrine, despite similar increases in end-systolic stress for all groups. There is an age- and hypertension-related decrease in reflex vagal restraint in response to α 1-adrenoceptor stimulation in humans, which leads to significant attenuation of the decrease in heart rate as well as in LV function in response to a pressor stimulus, and presumably therefore to enhanced systolic BP responses relative to young normotensive subjects.

Interaction of hypoxia and aging in the heart: analysis of high energy phosphate content.

To test the hypotheses that aged myocardium has lower ATP concentration and that a greater ATP hydrolysis during hypoxia exaggerates diastolic dysfunction in aged myocardium, we used 31P NMR spectroscopy to measure ATP and phosphocreatine (PCr) contents combined with heart function at baseline and during hypoxia and reoxygenation in perfused hearts isolated from young adult (3-4 months old) and old (24-25 months old) Fisher 344 rats. At baseline, old hearts had 30% lower heart rate and prevalent supraventricular arrhythmia; they had lower PCr and creatine contents (approximately 30%) but normal ATP content. Hypoxia caused similar decreases in heart rate and rate pressure product in young and old hearts. There was a two-fold increase in left-ventricular end-diastolic pressure (LVEDP) in young adults, but, surprisingly, no change in LVEDP in old hearts. ATP decreased similarly in hearts from young and old rats, but the PCr decrease was two-fold smaller in old hearts during hypoxia. Superimposition of pacing on hypoxic old hearts caused six-fold increase in LVEDP; although utilization of PCr increased, it was still incomplete. We conclude that PCr is incompletely used to maintain ATP level during hypoxia especially in the senescent heart, and that the increase in LVEDP in old hearts cannot be explained solely by changes in indices of bioenergetics.

Differential Activation of Cardiac and Peripheral Sympathetic Nervous System by Nifedipine: Role of Pharmacokinetics

Objectives. We sought to study the effects of short-acting and long-acting nifedipine on the sympathetic nervous system (SNS), heart rate (HR) and blood pressure (BP) of normotensive subjects under baseline conditions and during SNS stimulation.Background. Calcium channel antagonists in different pharmacokinetic formulations are widely used in patients with coronary artery disease or hypertension. Short-acting formulations activate the SNS, an action that may be disadvantageous in patients with coronary disease, especially if left ventricular function is impaired. The effects of slow-release formulations on the SNS are unknown.Methods. We used microneurography to investigate the influence of nifedipine (5 mg; 10 mg; and slow-release [GITS], 60 mg) on muscle sympathetic nerve activity (MSA) and skin sympathetic nerve activity (SSA) in healthy volunteers.Results. Peak plasma levels after short-acting and slow-release nifedipine were achieved within 60 min and 330 min, respectively. Short-acting (10 mg, n = 10) and slow-release (n = 10) nifedipine, but not placebo, markedly activated MSA and increased plasma norepinephrine; plasma endothelin increased only with slow-release nifedipine. HR increased after short-acting nifedipine, but not after nifedipine GITS. Nifedipine had no effect on SSA (n = 6). Blockade of cardiac sympathetic activity (with esmolol) led to similar decreases in HR with or without nifedipine, whereas parasympatholysis (with atropine) led to similar increases in HR with or without nifedipine. The cold pressor test markedly increased MSA in all treatment groups and further increased MSA beyond the increase induced by nifedipine.Conclusions. Nifedipine markedly increased MSA, but not SSA, independently of drug release formulation. In contrast, HR increased with short-acting, but not with slow-release, nifedipine. Therefore, nifedipine activates cardiac and peripheral sympathetic nerves differently depending on pharmacokinetics. These effects of nifedipine may be disadvantageous in cardiac patients with increased sympathetic activity or congestive heart failure, or both.(J Am Coll Cardiol 1997;29:1607–14)

Pharmacokinetics and Pharmacodynamics of Nefazodone and Propranolol Co-administration

Eighteen healthy male subjects received the following treatments (Q12h for 6.5 days) in randomized order with 14 day washout between periods: nefazodone 200 mg (NEF), propranolol 40 mg (PRO), and co-administration of NEF and PRO (NEF/PRO). Measurements of heart rate (HR) and systolic blood pressure for calculation of double product (DP= HRxSBP), an index of cardiac oxygen demand, were obtained prior to, during and after exercise on a treadmill using a multistage graded exercise protocol on Days 1 (pretreatment) and 6 (2 hr post dose) of each leg. Pharmacokinetics (PK) were evaluated on Day 7. There was no significant effect of NEF treatment on HR or DP compared to pretreatment. PRO and NEF/PRO produced similar decreases in HR at rest and during the exercise protocol. NEF/PRO reduced pre-exercise DP by 21% which was not different than PRO. However, post-exercise DP with NEF/PRO was decreased 40%, compared with the 23% decrease produced by PRO (p<0.05). This difference is not considered clinically significant. There was no effect of co-administration on PK of nefazodone and two metabolites, hydroxynefazodone and triazole dione. However, the AUC0-12 and Cmax of mCPP were increased by 28% and 22% with co-administration. Furthermore, the Cmax and AUC0-12 of propranolol were 30% and 14% lower with NEF/PRO than with PRO, however, there was no change in T-half. Similar changes in the PK of 4-OH propranolol were observed. In conclusion, co-administration of NEF and PRO caused modest changes in the PK of mCPP, propranolol and 4-hydroxypropranolol. However, the suppression of exercise-induced tachycardia and DP produced by PRO were not significantly affected by NEF. Thus, the PK inequivalencies are not clinically significant. Therefore, no change in initial dose of either drug is necessary and dose adjustments should be made on the basis of clinical response.

Absence of beneficial effect of intravenous metoprolol given during angioplasty in patients with single-vessel coronary artery disease

In a double-blind, randomized, placebo-controlled trial, the possible anti-ischemic effect of metoprolol during percutaneous transluminal coronary angioplasty was tested. Electrocardiograms, hemodynamics, and metabolism were studied in 27 patients with a stenosis in the left anterior descending coronary artery. Measurements took place before angioplasty, after each of four 1-minute occlusions and 15 minutes after the last balloon deflation. Patients were randomly given placebo or metoprolol (15 mg as a bolus intravenously, followed by an infusion of 0.04 mg/kg/hr). At the end of the procedure, the rate-pressure product had decreased by 15% (NS) and 23% (p = 0.001) in the placebo and metoprolol groups, respectively, mainly due to similar decreases in heart rate. Metoprolol tended to lower chest pain and reduce precordial ST-segment elevation due to angioplasty, but the effects were not statistically significant. Lactate, hypoxanthine, and urate release immediately after deflation was similar in both groups. Metoprolol reduced arterial plasma hypoxanthine throughout the procedure by about 30% (p < or = 0.02 vs. placebo). Thus, intravenous infusion of metoprolol did not significantly attenuate chest pain and ST-segment elevation, and failed to decrease cardiac lactate and oxypurine release. It did, however, reduce arterial hypoxanthine concentrations during angioplasty, possibly indicating that the beta-blocker inhibits extracardiac ATP catabolism.

Hemodynamic evaluation of bisoprolol after coronary artery surgery in patients with altered left ventricular function

Bisoprolol is a new cardioselective beta1 adrenergic blocking agent without intrinsic sympathomimetic activity but with minimal effects on myocardial contractility. Bisoprolol was compared to propranolol in 24 patients after cardiac surgery for coronary artery bypass graft (CABG). Each patient had been treated preoperatively with beta-blocking agents and had a cineangiographic left ventricular ejection fraction between 35% and 55%. Patients were randomized to receive orally either 10 mg of propranolol three times a day or 5 mg of bisoprolol once a day. Both drugs resulted in a significant and similar decrease in heart rate. This was associated with significant decreases in cardiac index, stroke index, and thermodilution right ventricular ejection fraction 6 hours after administration of propranolol, but not after bisoprolol. Systolic function measured by Doppler techniques significantly increased in the 10 postoperative days in patients under bisoprolol but not significantly after propranolol. Each drug was well tolerated during the 10 postoperative days, and the recovery was uneventful in each patient. These results indicate that in patients with altered systolic function after CABG, bisoprolol is susceptible to reduce heart rate with less cardiovascular alteration than propranolol.

Abnormal pressor response to vasopressin in patients with cirrhosis: Evidence for impaired buffering mechanisms

In patients with cirrhosis, vasopressin infusion induces sustained vasoconstriction and elevation of arterial pressure. The vasopressor effect could be caused by impairment of mechanisms normally aimed at buffering increases in arterial pressure (reflex bradycardia and decreases in arteriolar resistance). We studied the acute effects of continuous vasopressin infusion (0.4 IU/min) on systemic hemodynamics in seven patients with cirrhosis and in six patients without cirrhosis (controls). Vasopressin effects on systemic O2 consumption were also studied. In both groups, vasopressin infusion induced similar peak increases in arterial pressure, followed by similar decreases in heart rate and cardiac output. However, cirrhotic patients and controls differed 30 min after the start of vasopressin infusion. At 30 min, mean arterial pressure, diastolic arterial pressure and systemic vascular resistance remained significantly higher than preinfusion values in patients with cirrhosis. No decrease in systemic O2 consumption occurred in cirrhotic patients. In controls, at 30 min, mean arterial pressure and diastolic arterial pressure had returned to baseline. Systemic vascular resistance was not significantly higher than the preinfusion value and systemic O2 consumption had significantly decreased to below preinfusion values. We conclude that the vasopressor effect of vasopressin is abnormally sustained in patients with cirrhosis. This might be caused by insufficient buffering of vasopressin-induced arteriolar constriction rather than by abnormal vagal control of heart rate. In turn, as suggested by the lack of a decrease in systemic O2 consumption, persistent arteriolar constriction might be related to abnormally sustained sympathetic vascular tone in patients with cirrhosis.

Effect of head-out water immersion on response to exercise training.

During spaceflight and head-out water immersion (WI) there is a cephalad shift in blood volume. We have recently shown that left ventricular end-diastolic dimension is significantly greater during moderate cycling exercise with WI compared with on land. The purpose of this study was to determine whether the cephalad shift in blood volume and accompanying increase in cardiac preload with WI alters the normal cardiovascular adaptations to aerobic exercise training. Nine middle-aged healthy men trained on cycle ergometers in water, nine trained on land, and four served as controls for 12 wk. Following training, both training groups showed similar increase (P less than 0.05) in stroke volume and similar decreases in heart rate (P less than 0.01) and blood pressure (P less than 0.05) at a given submaximal exercise O2 consumption (VO2). Maximal VO2 increased (P less than 0.01) similarly for both training groups. The control group did not demonstrate any significant changes in submaximal or maximal exercise responses. We conclude that the cephalad shift in blood volume with WI does not alter the normal cardiovascular adaptation to aerobic exercise training.

Effects of three bradycardiac drugs on regional myocardial blood flow and function in areas distal to a total or partial coronary occlusion in dogs.

The effectiveness of three bradycardiac drugs for increasing distal coronary perfusion pressure and decreasing stenosis resistance (SR) in partially occluded vessels, and thereby for increasing collateral blood flow and segmental function (%SS) in an occluded area dependent on the stenotic vessel, was studied in anesthetized dogs. Initially, the distal portion of the left anterior descending (LAD) coronary artery was occluded followed by subsequent stenosis of the left circumflex (LC) coronary artery that supplies collateral flow to the ischemic LAD area. A decrease in LC flow (35 +/- 3 to 24 +/- 3 ml/min) and distal coronary pressure (109 +/- 4 to 47 +/- 4 mm Hg) resulted in an increase in SR (0.03 +/- 0.02 to 2.97 +/- 0.53 U), and decreases in LC %SS (9.3 +/- 1.1% to 1.9 +/- 2.0%), subendocardial blood flow (1.11 +/- 0.06 to 0.43 +/- 0.05 ml/min/g), and LAD collateral flow (0.36 +/- 0.11 to 0.22 +/- 0.05 ml/min/g). Upon intravenous administration on the beta-receptor-blocking drug sotalol (0.3 mg/kg) or metoprolol (0.1 mg/kg) and the non-beta-blocking bradycardiac drug N-dimethyl-propranolol (5.0 mg/kg) in doses that produced similar decreases in heart rate (30 to 40 beats/min), distal coronary pressure, subendocardial blood flow, and %SS in the LC area were markedly improved. SR was significantly reduced (2.97 +/- 0.53 to 1.66 +/- 0.37 U). The improvement in %SS of the LC area was highly correlated (r = .93, p less than .001) with the increase in subendocardial blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

COMPARATIVE EFFECTS OF PROPRANOLOL AND PRACTOLOL IN THE EARLY STAGES OF EXPERIMENTAL CANINE MYOCARDIAL INFARCTION

1 The effects of propranolol and practolol, at equivalent myocardial beta-adrenoceptor blocking doses, (as assessed by the degree of shift of isoprenaline dose-response curves) were investigated in anaesthetized greyhounds before and after acute coronary artery ligation. 2 When administered intravenously to the intact close-chest dog, propranolol (0.1 mg/kg) and practolol (0.5 mg/kg) caused similar decreases in heart rate, left ventricular dP/dt max, myocardial blood flow and cardiac output. Only propranolol increased peripheral vascular resistance. 3 When administered 2-3h after acute coronary artery ligation, propranolol (0.1 mg/kg) significantly decreased blood flow in both normally perfused and ischaemic regions of the heart. There was also electrocardiographic evidence of further deterioration after propranolol; two out of seven animals died following this treatment. 4 Practolol (0.5 mg/kg) when administered after coronary artery ligation also decreased normal myocardial blood flow but flow in the ischaemic area remained unchanged. Evidence was obtained from electrocardiographic, myocardial temperature, myocardial O2 consumption and lactate measurements that the administration of practolol, in contrast to propranolol, benefited the ischaemic myocardium. 5 Analysis of the results suggests that this beneficial action of practolol may be related to at least two mechanisms. Firstly the ability of practolol to increase the period during diastole when perfusion of the subendocardium is possible, without decreasing the transventricular pressure during this period. Secondly that practolol does not unmask alpha-adrenoceptor vasoconstriction in the ischaemic region.